Patent EA-000598-B1 (EA)
Title: Protein kinase c inhibitors
Inventor: HEATH WILLIAM F JN
IPC: A61K31/407
Filed: 1996-03-28
Abstract: 1. A compound of formula:   wherein: W is O, -S-, or NH; R1 is independently hydrogen, halo, C1-C4 alkyl, hydroxy, C1-C4 alkoxy, haloalkyl, nitro, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, or -NHCO(C1-C4 alkyl); R2 is hydrogen, CH3CO-, NH2, or hydroxy; Z is -(CH2)p- or -(CH2)p-O-(CH2)p-; R6 is -NH(CF3) or -N(CF3)(CH3); m is independently 0, 1, 2, or 3; and p is independently 0, 1 or 2; or a pharmaceutically acceptable salt or solvate thereof. 2. A compound of Claim 1 wherein R2 is hydrogen. 3. A compound of Claim 2 wherein W is a -O-. 4. A compound of Claim 3, which is of the formula:   wherein Z is -CH2-; R6 is -NHCF3) or N(CF3)(CH3). 5. A method for treating diabetes mellitus and its complications, which comprises administering to a mammal in need of such treatment a therapeutic amount of a compound of any one of Claims 1 through 4. 6. A method of inhibiting protein kinase C, which comprises administering to a mammal in need such treatment a pharmaceutically effective amount of a compound of any one of Claim 1 through 4. 7. A method for treating central ischemia brain injury, which comprises administering to a mammal in need of such treatment a therapeutic amount of a compound of any one of Claim 1 through 4. 8. A method for creating cardiovascular ischemia, which comprises administering co a mammal in need of such treatment a therapeutic amount of a compound of any one of Claims 1 through 4. 9. A method for treating inflammation, which comprises administering to a mammal in need of such treatment a therapeutic amount of a compound, of any one of Claims 1 through 4. 10. A method for treating restenosis, which comprises administering <=o a mammal in need of such treatment a therapeutic amount of a compound of any one of Claims 1 through 4. 11. A method for treating atherosclerosis, which comprises administering to a mammal in need of such treatment a therapeutic amount of a compound of any one of Claims 1 through 4. 12. A method for treating psoriasis, which comprises administering to a mammal in need of such treatment a therapeutic amount of a compound of any one of Claims 1 through 4. 13. A method for treating Alzheimer's disease, which comprises administering to a mammal in need of such treatment a therapeutic amount of a compound of any one of Claims 1 through 4. 14. A method for treating cancer, which comprises administering to a mammal in need of such treatment a therapeutic amount of a compound of any one of Claims 1 through- 4. 15. A pharmaceutical formulations comprising a compound of any one of Claims 1 through 4 together with one or more pharmaceutically acceptable excipients, carriers, or diluents. 16. A process of preparing a compound of any one of Claims 1 through 4, which comprises reacting a compound of the formula:   wherein: V is -O- or N-CH3; W is O, -S-, or -NH; R1 is independently hydrogen, halo, C1-C4 alkyl, hydroxy, C1-C4 alkoxy, haloalkyl, nitro, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2 or -NHCO(C1-C4 alkyl); Z is -(CH2)p- or -(CH2)p -O-(CH2)p; R6 is -NH(CF3) or -N(CF3)(CH3); m is independently 0, 1, 2, or 3; and p is independently 0, 1 or 2. with an excess of a mixture of a reagent and a C1-C4 alcohol in an polar aprotic solvent, said reagent being selected from hexamethyldisilazane or an ammonium salt. 17. A compound of formula   wherein W is O, -S-, or -NH; R1 is independently hydrogen, halo, C1-C4 alkyl, hydroxy, C1-C4 alkoxy, haloalkyl, nitro, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2 or -NHCO(C1-C4 alkyl); R2 is hydrogen, CH3CO-, NH2, or hydroxy; Z is -(CH2)p- or -(CH2)p -O-(CH2)p; R6 is -NH(CF3) or -N(CF3)(CH3); m is independently 0, 1, 2, or 3; and p is independently 0, 1 or 2, or pharmaceutically acceptablle salt or solvate thereof for use as a pharmaceutical.